A prospective multicenter clinical research study validating the effectiveness and safety of a chest X-ray-based pulmonary tuberculosis screening software JF CXR-1 built on a convolutional neural network algorithm

BackgroundChest radiography (chest X-ray or CXR) plays an important role in the early detection of active pulmonary tuberculosis (TB). In areas with a high TB burden that require urgent screening, there is often a shortage of radiologists available to interpret the X-ray results. Computer-aided detection (CAD) software employed with artificial intelligence (AI) systems may have the potential to solve this problem.ObjectiveWe validated the effectiveness and safety of pulmonary tuberculosis imaging screening software that is based on a convolutional neural network algorithm.MethodsWe conducted prospective multicenter clinical research to validate the performance of pulmonary tuberculosis imaging screening software (JF CXR-1). Volunteers under the age of 15 years, both with or without suspicion of pulmonary tuberculosis, were recruited for CXR photography. The software reported a probability score of TB for each participant. The results were compared with those reported by radiologists. We measured sensitivity, specificity, consistency rate, and the area under the receiver operating characteristic curves (AUC) for the diagnosis of tuberculosis. Besides, adverse events (AE) and severe adverse events (SAE) were also evaluated.ResultsThe clinical research was conducted in six general infectious disease hospitals across China. A total of 1,165 participants were enrolled, and 1,161 were enrolled in the full analysis set (FAS). Men accounted for 60.0% (697/1,161). Compared to the results from radiologists on the board, the software showed a sensitivity of 94.2% (95% CI: 92.0–95.8%) and a specificity of 91.2% (95% CI: 88.5–93.2%). The consistency rate was 92.7% (91.1–94.1%), with a Kappa value of 0.854 (P = 0.000). The AUC was 0.98. In the safety set (SS), which consisted of 1,161 participants, 0.3% (3/1,161) had AEs that were not related to the software, and no severe AEs were observed.ConclusionThe software for tuberculosis screening based on a convolutional neural network algorithm is effective and safe. It is a potential candidate for solving tuberculosis screening problems in areas lacking radiologists with a high TB burden

Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population.</p> <p>Methods</p> <p>The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system.</p> <p>Results</p> <p>As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA_{(rs8087945-rs12456774)}, haplotypes AG_{(rs8087945-rs12456774)}and GA_{(rs8087945-rs12456774)}were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively.</p> <p>Conclusions</p> <p>Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.</p

Effectiveness and safety of oseltamivir for treating influenza: an updated meta-analysis of clinical trials

<div><p></p><p><i>Background:</i> Oseltamivir has been widely used to treat patients with influenza; however, its effects have been debated. Recently, a new meta-analysis on the controversial topic of oseltamivir’s effectiveness found that the drug reduces the duration of influenza symptoms and the risk of hospitalization, while increasing the risk of nausea and vomiting. Unfortunately, the analysis did not include articles published in Chinese. Thus, we performed an updated meta-analysis by adding more studies in China. <i>Methods:</i> The terms ‘oseltamivir,’ ‘influenza,’ and ‘effect’ were used to search for publications in both English and Chinese. Only controlled clinical trials were included. We used the weighted mean difference (WMD) or relative risk (RR), together with the 95% confidence interval (95% CI), to estimate the effects of oseltamivir. <i>Results:</i> A total of 12 studies including 107 712 patients were eligible for analysis. Oseltamivir significantly reduced the duration of fever (WMD, –20.48; 95% CI, –28.43, –12.53) and influenza-like symptoms (WMD, –19.39; 95% CI, –32.94, –5.84). The rates of hospitalization (RR, 0.79; 95% CI, 0.68, 0.90), antibiotics usage (RR, 0.56; 95% CI, 0.42, 0.74), otitis media (RR, 0.78; 95% CI, 0.65, 0.93), and nonspecific complications (RR, 0.58; 95% CI, 0.35, 0.95) were significantly decreased among patients taking oseltamivir. No significant difference was observed with respect to the risk of adverse reactions. <i>Conclusion:</i> Oseltamivir can effectively alleviate the symptoms of influenza and reduce hospitalization, antibiotic usage, and the risk of otitis media without significantly increasing the rate of adverse drug reactions.</p></div

Is tuberculosis treatment really free in China? A study comparing two areas with different management models.

China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China.There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs.The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983-6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs.Under the current "free of diagnosis and treatment" policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients

Systolic blood pressure and recurrent stroke in patients with different lesion patterns on diffusion weighted imaging

Abstract Little is known about the relationship between baseline systolic blood pressure (SBP) and subsequent clinical events in patients with different lesion patterns on diffusion weighted imaging (DWI). We analyzed the Acute Non‐disabling Cerebrovascular Events (CHANCE) trial dataset. Patients were categorized into negative DW imaging (no detectable lesions), lacunar infarction (single lesion ≤15 mm) and non‐lacunar infarction (single lesion >15 mm or multiple lesions) based on lesion patterns on DWI. The primary outcome was recurrent stroke within 90 days. Cox proportional hazards models were used to assess the association between SBP levels and stroke outcomes in patients with different lesion patterns. A total of 1089 patients were analyzed. We found 258 cases (23.7%) with negative DW imaging, 392 (36.0%) with lacunar infarction and 439 (40.3%) with non‐lacunar infarction. Patients with non‐lacunar infarction had the highest incidence of stroke at 90‐day (P < .001). In non‐lacunar infarction group, compared with SBP < 160 mmHg, patients with SBP ≥ 160 mmHg had significantly higher risk of 90‐day recurrent stroke (20.3% vs. 10.7%; adjusted hazard ratio 1.81, 95% confidence interval 1.09–3.00). No significant association was found between SBP and clinical outcomes in patients with negative DWI and lacunar stroke groups. The result at 1 year was similar as at 90‐day. Therefore, non‐lacunar infarction, the most common lesion pattern in CHANCE study, had the highest risk of recurrent stroke and combined vascular events both in 90 days and 1 year. High baseline SBP was significantly associated with increased risk of short‐ and long‐term recurrent strokes in patients with non‐lacunar infarction

Multivariate linear regression analysis on factors related to the total out-of-pocket costs^*.

<p>*Total out-of-pocket costs was logarithmically transformed</p><p>Multivariate linear regression analysis on factors related to the total out-of-pocket costs^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126770#t005fn001" target="_blank">*</a>}.</p

A NMDA-receptor calcium influx assay sensitive to stimulation by glutamate and glycine/D-serine

N-methyl-D-aspartate-receptors (NMDARs) are ionotropic glutamate receptors that function in synaptic transmission, plasticity and cognition. Malfunction of NMDARs has been implicated in a variety of nervous system disorders, making them attractive therapeutic targets. Overexpression of functional NMDAR in non-neuronal cells results in cell death by excitotoxicity, hindering the development of cell-based assays for NMDAR drug discovery. Here we report a plate-based, high-throughput approach to study NMDAR function. Our assay enables the functional study of NMDARs with different subunit composition after activation by glycine/D-serine or glutamate and hence presents the first plate-based, high throughput assay that allows for the measurement of NMDAR function in glycine/D-serine and/or glutamate sensitive modes. This allows to investigate the effect of small molecule modulators on the activation of NMDARs at different concentrations or combinations of the co-ligands. The reported assay system faithfully replicates the pharmacology of the receptor in response to known agonists, antagonists, positive and negative allosteric modulators, as well as the receptor’s sensitivity to magnesium and zinc. We believe that the ability to study the biology of NMDARs rapidly and in large scale screens will enable the identification of novel therapeutics whose discovery has otherwise been hindered by the limitations of existing cell based approaches